Use of non-formulary drugs in children at a Brazilian teaching hospital: a descriptive study
Main Article Content
Keywords
Drug Utilization Review, Off-Label Use, Inpatients, Child, Brazil
Abstract
Objectives: To characterise the prescription of non-formulary drugs to children and neonates at a Brazilian teaching hospital and identify adverse drug reactions (ADRs), drug interactions, and prescription of potentially hazardous medicines.
Methods: A prospective exploratory study was carried out between January and May 2011 at the general paediatric wards and paediatric oncology, paediatric intensive care, and neonatal care units of the study hospital. Non-formulary drugs were categorised as approved, off-label, or not approved for use in children according to Brazilian compendia. Electronic health records were actively searched for ADRs and the possibility of moderate to severe interactions between non-formulary drugs and other medicines was determined with the Micromedex® database.
Results: Overall, 109 children or neonates received non-formulary drugs. Of these drugs, 54% were approved for use in children, 12.2% were used off-label, and 33.8% were not approved for use in children. Non-formulary drugs accounted for 13.4% of total prescriptions; 5.3% of drugs had a potential for interactions and five were possibly associated with ADRs.
Conclusion: Prescription of non-formulary drugs not approved for use in children was common at the study hospital. Studies such as this provide information on the use of medicines for special indications and permit assessment of the relevance of hospital formularies for the paediatric population.
References
2. Brassica, SC. O Papel do Farmacêutico na Utilização de Medicamentos Não Aprovados e em Indicações Não Licenciadas. In: Farmácia Clínica e Atenção Farmacêutica (Guanabara Koogan,ed), Rio de Janeiro. 2008; p.221-5.
3. Ribeiro E, Takagi CA. Seleção de Medicamentos. In: Farmácia Clínica e Atenção Farmacêutica (Guanabara Koogan, ed), Rio de Janeiro. 2008; p.136-44.
4. Kairuz TE, Gargiulo D, Bunt C, Garg S. Quality, Safety and Efficacy in the ‘Off-Label’ Use of Medicines. Curr Drug Saf. 2007;2(1):89-95.
5. Delgado O, Puigventós F, Clopés A. [Position of the hospital pharmacist regarding the use of medication in non-authorised conditions]. Farm Hosp. 2009;33(5):237-9.
6. Macaulay TE, Cook AM, Fink JL 3rd, Rapp RP, Vincent WR 3rd. Pharmacists’ role in facilitating evidence-based prescribing for unlabeled use of medications. Am J Health Syst Pharm. 2009;66(19):1735-9. doi: 10.2146/ajhp080352.
7. Boots I, Sukhai RN, Klein RH, Holl RA, Wit JM, Cohen AF, Burggraaf J. Stimulation Programs for Pediatric Drug Reserch – Do Children Really Benefit? 2007; Eur J Pediatr. 2007;166(8):849-55.
8. Santos DB, Clavenna A, Bonati M, Coelho HL. Off-label and unlicensed drug utilization in hospitalized children in Fortaleza, Brasil. Eur J Clin Pharmacol. 2008;64(11):1111-8. doi: 10.1007/s00228-008-0543-1.
9. Carvalho PR, Carvalho CG, Alievi PT, Martinbiancho J, Trotta EA. Prescription of Drugs not Appropriate for Children in a Pediatric Intensive Care Unit. J Pediatr (Rio J). 2003;79(5):397-402.
10. Dos Santos L, Heineck I. Drug Utilization Study in Pediatric Prescriptions of a University Hospital in Southern Brazil: Off-label, Unlicensed and High-alert Medications. Farm Hosp. 2012;36(4):180-6. doi: 10.1016/j.farma.2010.12.008.
11. Cuzzolin L, Atzei A, Fanos V. Off-label and unlicensed prescribing for newborns and children in different settings: review of the literature and a consideration about drug safety. Expert Opin Drug Saf. 2006;5(5):703-18.
12. Clavenna A, Bonati M. Adverse drug reactions in childhood: a review of prospective studies and safety alerts. Arch Dis Child. 2009;94(9):724-8. doi: 10.1136/adc.2008.154377.
13. Dell'Aera M, Gasbarro AR, Padovano M, Laforgia N, Capodiferro D, Solarino B, Quaranta R, Dell'Erba AS. Unlicensed and off-label use of medicines at a neonatology clinic in Italy. Pharm World Sci. 2007;29(4):361-7.
14. Food and Drug Administration (2000) Guidance for industry E11. Clinical investigation of medicinal products in the pediatric population. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologies Evaluation an Reasearch (CBER), p. 9-12.
15. Drugdex – Micromedex Healthcare series. V. 1.0. New York: Thomson Healthcare, Inc. 1974-2010. Available at http://www.portaldapesquisa.com.br/databases/sites (Access: Jan – May 2011).
16. Institute for Safe Medication Practices (2008); Lista de Medicamentos Potencialmente. Perigosos. Available at http//www.ismp.org/Tools/highalertmedications.pdf (Access: Oct. 2010).
17. Conroy S, McIntyre J. The use of unlicensed and off-label medicines in the neonate. Semin Fetal Neonatal Med. 2005;10(2):115-22.
18. Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, Knoeppel C, Seyberth H, Pandolfini C, Raffaelli MP, Rocchi F, Bonati M, Jong G, de Hoog M, van den Anker J. Survey of unlicensed and off-label drug use in paediatric wards in European countries. BMJ. 2000;320(7227):79-82.
19. 't Jong GW, van der Linden PD, Bakker EM, van der Lely N, Eland IA, Stricker BH, van den Anker JN. Unlicensed and off-label drug in paediatric ward of a general hospital in the Netherlands. Eur J Clin Pharmacol. 2002;58(4):293-7.
20. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ.A method for estimating the probability of adverse drug reaction. Clin Pharmacol Ther. 1981;30(2):239-45.
21. Rawlings MD, Thompson JW. Mechanism of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions, 4th edn. Owford Oxford Medical publication , 1991: Chapter 3.
22. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual dos centros de referência dos imunobiológicos especiais – Brasília: Ministério da Saúde, 2006. 188 p
23. Kimland E, Nydert P, Odlind V, Böttiger Y, Lindemalm S. Paediatric drug use with focus on off-label prescriptions at Swedish hospitals – a nationwide study. Acta Paediatr. 2012;101(7):772-8. doi: 10.1111/j.1651-2227.2012.02656.x.
24. Hsien L, Breddemann A, Frobel AK, Heusch A, Schmidt KG, Läer S. Off-label drug use among hospitalised children: identifying areas with the highest need for research. Pharm World Sci. 2008;30(5):497-502. doi: 10.1007/s11096-008-9193-8.
25. Sepúlveda-Vildósola AC, Betanzos-Cabrera Y, Lastiri GG, Rivera-Márquez H, Villasis-Keever MA, Del Angel VW, Díaz FC, López-Aguilar E. Palonosetron Hydrochloride Is an Effective and Safe Option to Prevent Chemotherapy-induced Nausea and Vomiting in Children. Arch Med Res. 2008;39(6):601-6. doi: 10.1016/j.arcmed.2008.04.007.
26. Gore L, Chawla S, Petrilli A, Hemenway M, Schissel D, Chua V, Carides AD, Taylor A, Devandry S, Valentine J, Evans JK, Oxenius B; Adolescent Aprepitant in Cancer Study Group. Aprepitant in Adolescent Patients for Prevention of Chemotherapy-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Tolerability. Pediatr Blood Cancer. 2009;52(2):242-7. doi: 10.1002/pbc.21811.
27. van den Berg H, Tak N.Licensing and labelling of drugs in a paediatric oncology ward. Br J Clin Pharmacol. 2011;72(3):474-81. doi: 10.1111/j.1365-2125.2011.03977.x.
28. Conroy S, Newman C, Gudka S. Unlicensed and off-label drug use in acute lymphoblastic leukaemia and other malignancies in children. Ann Oncol. 2003;14(1):42-7.
29. O'Donnell CP, Stone RJ, Morley CJ. Unlicensed and off-label drug use in an Australian neonatal intensive care unit. Pediatrics. 2002;110(5):e52.
30. Gill AM, Leach HJ, Hughes J, Barker C, Nunn AJ, Choonara I.Adverse drug reactions in a paediatric intensive care unit. Acta Paediatr. 1995;84(4):438-41.
31. Santos DB, Coelho HLL. Reações adversas a medicamentos em pediatria: uma revisão sistemática de estudos prospectivos. Rev Bras Saúde Matern Infant. 2004;4:341-9
32. Lopez-Gonzalez E, Herdeiro MT, Figueiras A. Determinants of Under-Reporting of Adverse Drug Reactions a Systematic Review. Drug Saf. 2009;32(1):19-31. doi: 10.2165/00002018-200932010-00002.
33. Castro-Pastrana LI, Carleton BC.Improving pediatric drug safety: need for more efficient clinical translation of pharmacovigilance knowledge. J Popul Ther Clin Pharmacol. 2011;18:e76-88.
34. Silva Md, Rosa MB, Franklin BD, Reis AM, Anchieta LM, Mota JA. Concomitant prescribing and dispensing errors at a Brazilian hospital: a descriptive study. Clinics (Sao Paulo). 2011;66(10):1691-7.